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. 2021 Oct 29:12:725362.
doi: 10.3389/fphar.2021.725362. eCollection 2021.

Comparing the Effect of Piperine and Ilepcimide on the Pharmacokinetics of Curcumin in SD Rats

Peijian Wang  1 , Hui Li  1 , Zhexuan Lin  1 , Hongjun Luo  1 , Wenhong Luo  1
Affiliations

Comparing the Effect of Piperine and Ilepcimide on the Pharmacokinetics of Curcumin in SD Rats

Peijian Wang et al. Front Pharmacol. .

Abstract

The poor bioavailability and rapid metabolism of curcumin (CUR) restrict its clinical application. Piperine (PIP), which was extracted from natural compounds, can increase the plasma concentration of curcumin in humanidad. As an artificial synthetic piperine analog, silepcimide (ILE) has significant advantages because of the low price and simple synthesis process. In this study, a simple and rapid HPLC-UV method was developed for determination of the plasma concentration of CUR, PIP,ILE and dihydrocurcumin (DHC, a metabolite of CUR) simultaneously. Meanwhile, the effects of PIP and ILE on the plasma concentration and pharmacokinetics of DHC in SD rats was studied to explore whether ILE could serve as a CUR bioavailability enhancer. The metabolic pathway of CUR was studied by comparing the differences of CUR plasma concentration between intravenous injection and oral administration over the same time period, and reacting with small intestine homogenate without microbes of SD rats. The results of drug-time curve showed that combined administration of ILE and CUR had significant effect on plasma concentrations of DHC. Repeated administration of PIP or ILE could significantly increase the plasma concentration of DHC. Plasma CUR could be detected in the samples of from intravenous injection of CUR rats, whereas, it couldn't be detected in the plasma sample form oral administration rats. CUR incubated with intestinal homogenate without intestinal bacteria could not be transformed into DHC. In conclusion, our results show that ILE can improve the bioavailability of CUR. Additionally, it was inferred that most of the CUR was reduced to DHC by NADPH when it was absorbed from gastrointestinal tract, and our results demonstrated that this pathway might be mediated by gastrointestinal microorganisms.

Keywords: curcumin; dihydrocurcumin; ilepcimide; pharmacokinetics; piperine; plasma concentration.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Chemical construction of CUR, DHC, PIP and ILE.
FIGURE 2
FIGURE 2
Chromatogram of DHC and PIP in biological samples with ILE as internal standard. Detections of A, B, C were recorded at 420, 340, 323 nm.
FIGURE 3
FIGURE 3
Chromatogram of DHC and ILE in biological samples with PIP as internal standard. Detections of A, B, C were recorded at 420, 340, 323 nm.
FIGURE 4
FIGURE 4
Drug-time curve of DHC. Group of A: Group of CUR, Group of B: Group of CUR and PIP, Group of C: Group of CUR and ILE.
FIGURE 5
FIGURE 5
Drug-time curve of PIP.
FIGURE 6
FIGURE 6
Drug-time curve of ILE.
See this image and copyright information in PMC

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